RESUMO
Drug repositioning is a strategy for repurposing the approved or investigational drugs that are outside the scope of the original medical indication. Memantine is used as a noncompetitive NmethylDaspartate receptor antagonist to prevent glutamatemediated excitotoxicity in Alzheimer's disease, and is one of the promising agents which is utilized for the purpose of cancer therapy. However, the association between memantine and Golgi glycoprotein 1 (GLG1), an intracellular fibroblast growth factor receptor, in cancers has not yet been clarified. The present study analyzed the expression and location of GLG1 in tumor cells treated with memantine. Memantine was found to suppress the growth of malignant glioma and breast cancer cells in a concentrationdependent manner. The mRNA expression of GLG1 was upregulated in a concentrationdependent manner, and the splicing variant profiles were altered in all cell lines examined. The results of western blot analysis revealed an increase in the fulllength and truncated forms of GLG1. Moreover, GLG1 spread in the cytosol of memantinetreated cells, whereas it localized in the Golgi apparatus in control cells. Since GLG1 functions as a decoy FGF receptor, the modulation of GLG1 may prove to be one of the mechanisms underlying the cancersuppressive effects of memantine.
Assuntos
Doença de Alzheimer , Memantina , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Proteínas de Transporte/metabolismo , Humanos , Memantina/farmacologia , Memantina/uso terapêutico , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , Receptores de Fatores de Crescimento de Fibroblastos/metabolismo , Sialoglicoproteínas , Transdução de SinaisRESUMO
Arynes are found to be facilely inserted into bis(pinacolato)diboron by using a platinum-isocyanide catalyst, affording diverse 1,2-diborylarenes, which can be converted into o-terphenyls via Suzuki-Miyaura coupling reaction.